Scavenger receptors (SRs), commonly expressed on the surfaces of macrophages, vascular endothelium and certain dendritic cells, comprise a structurally diverse group of receptors that share the common theme of binding to modified lipoproteins. Biologically, SRs are important for the detection and clearance of a wide array of potentially harmful ligands such as oxidatively modified proteins and lipoproteins, advanced glycation end products (AGE), bacteria, anionic polymers, apoptotic cells, and foreign particles such as silica dust, asbestos and diesel exhaust particles. Particular attention has been focused on oxidized low density lipoprotein (oxLDL), an almost universal SR ligand thought to be significant in the pathology of atherosclerosis. We have begun structural investigations of three key SRs and are obtaining clones for several others. Our goal is to investigate the atomic structures and ligand recognition mechanisms of SRs using x-ray crystallography and various biophysical binding studies. This information is critical to elucidating how the innate immune system interfaces with and responds to both endogenous and environmental challenges. Currently we have high resolution x-ray data on one receptor and are analyzing its structure. Subcloning, design of multiple constructs, and receptor expression studies in E coli and baculovirus/insect cells are presently underway for several SRs.